The challenges of levodopa dosing and food intake

I receive many Ask the Doctor questions about food intake and levodopa ingestion, and I know it’s a tough balance for many. Instructions on how best to take levodopa can seem contradictory. On one hand, people with Parkinson’s disease (PD) are told to separate levodopa from food intake and take their medication doses either 30 minutes before or 1-2 hours after a meal. But this advice is not easily followed for a whole host of reasons:

• If a person is meant to take multiple doses of levodopa a day while trying to follow this advice, the timing of meals can become very challenging. Let’s say that a person takes their levodopa doses every 2 hours. After dose #1 is taken, then meal #1 can be eaten 30 minutes later. But then that person needs to wait 1-2 hours after the meal before taking the next dose, which then causes you to delay your next scheduled dose. The day becomes a chore of precisely measuring when doses can be taken and meals can be eaten.
• The above problem is compounded by the issue of weight loss, which can be an issue for some people with PD. How is a person meant to gain weight if there is such stress and limitation over when food can be eaten?
• Nausea, which is a common side effect of levodopa, especially when the medication is first started, is exacerbated if the medication is taken without food. For those who have nausea, how can levodopa be tolerated if it can’t be taken with food?

A second problem with eating and levodopa ingestion is for someone with advancing PD who may have swallowing difficulties but also may be prescribed levodopa doses multiple times a day. How is a person supposed to constantly be taking pills when they have trouble swallowing?

I will try to answer these questions and hopefully provide some guidance that could make your life easier.

Are there any foods to avoid when taking levodopa?

The first thing to note is that there is no danger in taking carbidopa/levodopa with any type of food. Any recommendations about food and levodopa intake are because, in some people, ingesting levodopa along with certain foods such as dietary protein can decrease the medication’s absorption into your bloodstream and brain and therefore decrease levodopa’s effectiveness.

Protein and levodopa

How levodopa interacts with high-protein foods

Some people with PD experience what is referred to as the “protein effect” in which dietary protein can interfere with absorption of levodopa.

Once dietary protein is eaten, it is broken down within the gut into its building blocks called amino acids. Amino acids come in different varieties and are grouped according to different chemical characteristics. One group is called the Large Neutral Amino Acids (LNAAs), which includes phenylalanine, tyrosine, and tryptophan. These amino acids all use the same transporter in the small intestine wall and in the blood brain barrier to shuttle them across the gut wall and into the bloodstream and across the blood vessel wall into the brain.

The problem is that levodopa uses this transporter as well. Therefore, if there are LNAAs in the small intestine or bloodstream when levodopa is also there, there may not be enough transporters available for the levodopa to get across the small intestine wall and into the bloodstream and brain.  If ingesting dietary protein decreases a person’s absorption of levodopa, this is referred to as “the protein effect.”

LNAAs are found in many sources of dietary protein including beef, pork, fish, chicken, tofu, milk, cheese, beans, seeds, nuts, and whole grains. These food sources differ in how much LNAAs they contain.

It is important to emphasize that the protein effect only occurs in a subset of people with PD, typically as the disease advances.  For many people, especially those in earlier stages of the disease, this is not an issue at all.  The transporter is not a limiting factor, with protein and levodopa crossing from the gut into the bloodstream and brain in a non-competitive fashion.

Therefore, if you find that the medication works well for you when you take it with food, even with foods rich in dietary protein, then you can continue doing what you are doing.

What if eating protein affects how well a dose of levodopa works?

If the protein effect does appear to be a problem for you, there are two ways to adjust your diet:

1. Ingest your daily protein at the end of the day, so that you do not have the protein effect during your active time. Take your levodopa doses as scheduled by your doctor, even if they are every two hours. Take your levodopa with food if that is necessary to prevent nausea. Eat foods that are rich in calories if weight loss is a problem for you. Eat your meals when you want to. Just make sure that the food that you ingest during your active time does not contain dietary protein. These foods could be carbohydrates, such as pasta, rice, and bread, or fruits and vegetables. Then, save your protein intake for the end of the day. Note: in this case, dietary protein at the end of the day is essential since proteins are the source of many vital components of your body and are essential for healthy living.
2. Divide your intake of protein evenly throughout the day so that all your meals contain the same amount of dietary protein. That way, the medication absorption should theoretically be similar throughout the day. To properly calculate this, it may be wise to seek the guidance of a registered dietician.

For those who do have the protein effect, using either of these rules above should make managing levodopa and food ingestion more attainable.

Many people ask: “How do I know if I have the protein effect?” The answer is, by trial and error. If a levodopa dose taken with protein is just as effective as one taken with carbohydrates, then you do not have the protein effect.

Of course, if you are not currently taking levodopa, then you can carry on with your normal intake of protein.

Issues with other foods and levodopa

Some people report a more comprehensive interaction between food intake and levodopa response. Their experience is that other foods besides those that are rich in protein can lead to poor absorption of their medication. If this is the case for you, consider keeping a strict food diary for a few days, recording exactly what you eat and when, the times that you take your medication, and your corresponding PD symptoms. You can then review this diary with your neurologist as well as a dietitian to try to discern what components of food are interfering with absorption of your medication.

Iron

Iron supplements can bind with levodopa and thereby reduce the amount of medication that is absorbed in your system. If you require iron supplementation because of another medical condition, discuss this with your doctor so you can determine how to most effectively get the iron you need while not impacting your PD medications.

Vitamin B6 and B12

Vitamin B6 interacts with both carbidopa and levodopa. Current understanding is that Vitamin B6 drives the conversion of levodopa to dopamine and carbidopa irreversibly binds Vitamin B6. For most people, eating a healthy diet and taking standard doses of oral carbidopa/levodopa will result in an appropriate balance between these compounds, normal levels of Vitamin B6 in the system, and good PD symptom control. 

However, if nutrition is poor or if a person takes high doses of oral carbidopa/levodopa, Vitamin B6 levels could be too low. Of note, those on carbidopa/levodopa intestinal gel or Duopa may be more at risk for Vitamin B6 deficiency than those on oral carbidopa/levodopa. Signs of Vitamin B6 deficiency can include anemia, depression, confusion, and even seizures. Vitamin B6 deficiency can also cause peripheral neuropathy which can result in numbness, tingling, and pain in the feet as well as balance issues. If there is any concern, Vitamin B6 levels in the blood can be checked and supplementation can be given.

Rarely an excess of Vitamin B6 in the system (by taking too much of a Vitamin B6 supplement for example) might drive too much levodopa conversion to dopamine in the periphery before it gets to the brain leading to poorer PD symptom control. Practically, this is only a concern if a person is taking levodopa without carbidopa. Overall, Vitamin B6 deficiency is more of a potential issue than Vitamin B6 excess.

Vitamin B12 is another key vitamin that shares metabolic pathways with Vitamin B6. Vitamin B12 deficiency is common in the aging population in general and may be even more common in people with PD. Vitamin B12 deficiency can cause a whole host of symptoms including fatigue, signs of peripheral neuropathy (numbness, tingling, pain, balance issues), memory problems, depression, and irritability. This article highlights the relationship between Vitamin B6, Vitamin B12, and Parkinson’s disease.

The bottom line is – talk with your neurologist about possibly checking your Vitamin B6 and Vitamin B12 levels. If they are low, talk with your doctor about how to take the appropriate supplementation.

How can I take levodopa when I also have swallowing difficulties?

Two formulations of carbidopa/levodopa are available that can be very helpful for those who have swallowing difficulties. Parcopa^®, is an orally disintegrating carbidopa/levodopa tablet. Parcopa comes in the same strengths as immediate-release carbidopa/levodopa and can therefore be exchanged easily. Rytary^® is carbidopa/levodopa extended-release capsules. The capsules contain beads of medication and can be opened and mixed with food, while retaining their extended-release qualities. The conversion from immediate-release carbidopa/levodopa to Rytary is not as straightforward as to Parcopa but can be done with the help of your doctor.

Bottom line, if you are having difficulty figuring out how taking your levodopa fits into your life – ask your doctor or other PD health care providers. There may be tricks you can use to make your life easier!

Tips and Takeaways

• In some people with PD, levodopa absorption can be affected by your food intake, particularly ingestion of dietary proteins found in beef, fish, chicken, etc. (this is called the “protein effect”)
• If the protein effect does not happen to you, you can eat anything you like and not worry about your medication doses
• If the protein effect is a problem for you, then try to reserve intake of dietary protein to the end of the day, or try to evenly space out your ingestion of protein throughout the day
• If swallowing difficulties interfere with levodopa dosing, ask your doctor about using Parcopa, an orally disintegrating form of carbidopa/levodopa; or Rytary, a carbidopa/levodopa capsule that can be opened and mixed with food
• With this, or any other issues/symptoms you may experience, it is always smart to address your concerns with your doctor because there could be some adjustments, tips, or tricks that can help improve your situation